Resistance-breaking strains of tomato spotted wilt virus hamper photosynthesis and protein synthesis pathways in a virus accumulation-dependent manner in Sw5-carrying tomatoes.

Tomato spotted wilt virus (TSWV; Orthotospovirus tomatomaculae) is one of the major horticultural threats due to its worldwide distribution and broad host range. In Italy, TSWV is widely spread in tomato (Solanum lycopersicum) crops and causes severe yield losses. In the last decades, several tomato varieties carrying the Sw-5b gene for resistance to TSWV have been released.

Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.

Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress.

Efficient nonlinear function approximation in analog resistive crossbars for recurrent neural networks.

Analog In-memory Computing (IMC) has demonstrated energy-efficient and low latency implementation of convolution and fully-connected layers in deep neural networks (DNN) by using physics for computing in parallel resistive memory arrays. However, recurrent neural networks (RNN) that are widely used for speech-recognition and natural language processing have tasted limited success with this approach. This can be attributed to the significant time and energy penalties incurred in implementing nonlinear activation functions that are abundant in such models.

Increased serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage.

Background: The immune heterogeneity of biliary atresia (BA) presents a challenge for development of prognostic biomarkers. This study aimed to identify early immune signatures associated with biliary drainage after Kasai Portoenterostomy (KPE).

Methods: Serum samples, liver slides, and clinical data were obtained from patients enrolled in the NIDDK-supported Childhood Liver Disease Research Network.

Outside-in engineering of cadherin endocytosis using a conformation strengthening antibody.

P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism.

Intricacies of human-AI interaction in dynamic decision-making for precision oncology.

AI decision support systems can assist clinicians in planning adaptive treatment strategies that can dynamically react to individuals' cancer progression for effective personalized care. However, AI's imperfections can lead to suboptimal therapeutics if clinicians over or under rely on AI. To investigate such collaborative decision-making process, we conducted a Human-AI interaction study on response-adaptive radiotherapy for non-small cell lung cancer and hepatocellular carcinoma.

Strength and durability of indirect protection against SARS-CoV-2 infection through vaccine and infection-acquired immunity.

Early investigation revealed a reduced risk of SARS-CoV-2 infection among social contacts of COVID-19 vaccinated individuals, referred to as indirect protection. However, indirect protection from SARS-CoV-2 infection-acquired immunity and its comparative strength and durability to vaccine-derived indirect protection in the current epidemiologic context of high levels of vaccination, prior infection, and novel variants are not well characterized. Here, we show that both vaccine-derived and infection-acquired immunity independently yield indirect protection to close social contacts with key differences in their strength and waning.

Precession modulates the poleward expansion of atmospheric circulation to the Arctic Ocean.

Under sustained global warming, Arctic climate is projected to become more responsive to changes in North Pacific meridional heat transport as a result of teleconnections between low and high latitudes, but the underlying mechanisms remain poorly understood. Here, we reconstruct subarctic humidity changes over the past 400 kyr to investigate the role of low-to-high latitude interactions in regulating Arctic hydroclimate. Our reconstruction is based on precipitation-driven sediment input variations in the Subarctic North Pacific (SANP), which reveal a strong precessional cycle in subarctic humidity under the relatively low eccentricity variations that dominated the past four glacial-interglacial cycles.

Academic Achievement, Externalizing Problems, and Close Friends in Middle School: Testing a Developmental Cascade Model Leading to Educational Attainment in the Late Twenties.

Because educational attainment is associated with well-being in the long term, it is important to understand the developmental processes that enhance academic outcomes during adolescence. Also, although the importance of friends is well documented in adolescence, little is known about how close friends' characteristics work together with youth's own characteristics to shape adolescents' educational trajectories. This study fills an important gap in knowledge by focusing on how middle school students' academic achievement and externalizing problems are associated with their friends' achievement and externalizing problems over time, and how these variables predict educational attainment in adulthood.

Engaging Patients in Discussions About Medication Deprescribing.

Background: Deprescribing, intentional medication discontinuation or dose reduction, can reduce potentially inappropriate medication use and medication-related harms. Engaging patients in deprescribing discussions may increase likelihood of deprescribing and promote shared decision-making.

Objective: To examine the impact of patient-directed educational brochures on patient engagement and deprescribing discussions with primary care providers (PCPs).

Comparison of Pharmacokinetics of Long-Acting Local Analgesics: CPL-01, a Novel Extended-Release Ropivacaine, Demonstrates Consistent and Predictable Exposure Compared with Liposomal Bupivacaine.

Background And Objective: There is a significant medical need for improved long-acting local anesthetics to decrease postsurgical pain and reduce postoperative opioid use. While ropivacaine is considered a safer local anesthetic than bupivacaine, no long-acting ropivacaine formulation is currently marketed. Available formulations of bupivacaine show inconsistent pharmacokinetics (PK) among different surgical models, and inconsistency in PK may lead to a reluctance to use the medication owing to fear of local anesthetic systemic toxicity (LAST) or unreliable efficacy.

Sources of Microstructure in Mammalian Cochlear Responses.

Quasiperiodic fluctuations with frequency are observed in a variety of responses that either originate from or strongly depend on the cochlea's active mechanics. These spectral microstructures are unique and stable features of individual ears and have been most thoroughly studied in behavioral hearing thresholds and otoacoustic emissions (OAEs). While the exact morphology of the microstructure patterns may differ across measurement types, the patterns are interrelated and are thought to depend on common mechanisms.

Triaging mammography with artificial intelligence: an implementation study.

Purpose: Many breast centers are unable to provide immediate results at the time of screening mammography which results in delayed patient care. Implementing artificial intelligence (AI) could identify patients who may have breast cancer and accelerate the time to diagnostic imaging and biopsy diagnosis.

Methods: In this prospective randomized, unblinded, controlled implementation study we enrolled 1000 screening participants between March 2021 and May 2022.

Bridging Gaps: Enhancing Sleep and Health Disparities in Latino Families with Young Adults with Autism Using a Culturally Adapted Intervention.

The present study examined the effects of a culturally adapted intervention, ¡Iniciando! la Adultez, on sleep and health-related quality of life (HRQoL) in Latino young adults with autism spectrum disorder (ASD) and their Spanish-speaking parents. The intervention targeted the transition to adulthood, a period associated with increased challenges in sleep and HRQoL, particularly for underserved Latino populations. Participants included 26 young adults and 38 parents who completed assessments at baseline and post-treatment.

Cadmium Pollution Deteriorates the Muscle Quality of Labeo rohita by Altering Its Nutrients and Intestinal Microbiota Diversity.

The detrimental effects of cadmium (Cd), a hazardous heavy metal, on fish have triggered global concerns. While the ecotoxicity of Cd on fish has been investigated, the impact of Cd on muscle quality and its correlation with the gut microbiota in fish remains scarce. To comprehensively uncover Cd effects based on preliminary muscle Cd deposition, relevant studies, and ecological Cd pollution data, we exposed Labeo rohita to Cd under concentrations of 0.

AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.

Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice.

Effectiveness and patient satisfaction with the new sildenafil oral suspension formulation compared to sildenafil oro-dispersible film: a real-life study.

Sildenafil is one of the most used phosphodiesterase type 5 inhibitor (PDE5i) for the treatment of erectile dysfunction (ED) in clinical practice. A new oral suspension formulation (OSF) of sildenafil has been introduced to overcome the drawbacks of previous formulations. We assess the efficacy and patients' experience with sildenafil 50 mg OSF in men with ED who were taking the sildenafil oro-dispersible film (ODF).

Medical management pathways for Cushing's disease in pituitary tumors centers of excellence (PTCOEs).

Purpose: A recent update of consensus guidelines for the management of Cushing's disease (CD) included indications for medical therapy. However, there is limited evidence regarding their implementation in clinical practice. This study aimed to evaluate current medical therapy approaches by expert pituitary centers through an audit conducted to validate the criteria of Pituitary Tumors Centers of Excellence (PTCOEs) and provide an initial standard of medical care for CD.

Ongoing Symptoms and Concerns Experienced by Low-Risk Breast Cancer Survivors Following Active Treatment.

Introduction: Little is known about the symptom burden of breast cancer survivors with early-stage disease. Many studies have focused on symptoms of patients who are undergoing or recently completed systemic therapy. However, with the increased use of Oncotype DX, the proportion of early-stage hormone receptor-positive patients who undergo chemotherapy has declined, making existing studies of the symptom experience less useful for these patients.

An evaporite sequence from ancient brine recorded in Bennu samples.

Evaporation or freezing of water-rich fluids with dilute concentrations of dissolved salts can produce brines, as observed in closed basins on Earth and detected by remote sensing on icy bodies in the outer Solar System. The mineralogical evolution of these brines is well understood in regard to terrestrial environments, but poorly constrained for extraterrestrial systems owing to a lack of direct sampling. Here we report the occurrence of salt minerals in samples of the asteroid (101955) Bennu returned by the OSIRIS-REx mission.

Expanding the human gut microbiome atlas of Africa.

Population studies provide insights into the interplay between the gut microbiome and geographical, lifestyle, genetic and environmental factors. However, low- and middle-income countries, in which approximately 84% of the world's population lives, are not equitably represented in large-scale gut microbiome research. Here we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,801 women from Burkina Faso, Ghana, Kenya and South Africa.

Engineered heart muscle allografts for heart repair in primates and humans.

Cardiomyocytes can be implanted to remuscularize the failing heart. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques.

Global meta-analysis shows action is needed to halt genetic diversity loss.

Mitigating loss of genetic diversity is a major global biodiversity challenge. To meet recent international commitments to maintain genetic diversity within species, we need to understand relationships between threats, conservation management and genetic diversity change. Here we conduct a global analysis of genetic diversity change via meta-analysis of all available temporal measures of genetic diversity from more than three decades of research.

Copper-dependent halogenase catalyses unactivated C-H bond functionalization.

Carbon-hydrogen (C-H) bonds are the foundation of essentially every organic molecule, making them an ideal place to do chemical synthesis. The key challenge is achieving selectivity for one particular C(sp)-H bond. In recent years, metalloenzymes have been found to perform C(sp)-H bond functionalization.